Tumor cells frequently synthesize and secrete proteins not normally present in body fluids. About 15 such tumor-related proteins have so far been isolated and characterized. Each has provided a useful tool for diagnosis and management of a particular type of cancer. We have now discovered the presence of a new series of such tumor-related proteins in the urine of patients with advanced cancer. The series seems to consist of about 8 to 10 glycoproteins, mol wt 10000-60000. So far 4 have been isolated. This line of work will advance cancer research in 2 ways. 1. Immunoassays to 3 of the 4 isolated members have already proven to be useful in early diagnoses of 2 types of localized cancer, in estimating the degree of spread in most types of disseminated cancer, and in predicting the timing of response and relapse of disseminated cancer patients who are receiving chemotherapy. When the entire series of glycoproteins has been isolated, the battery of 8 to 10 specfic immunoassays will provide a new approach to screening the population for early cancer and for monitoring the natural history of neoplastic disease. Moreover, measurement of the release of these glycoproteins by leukemic cells in vitro may provide a new way to select chemotherapy in advance for patients with acute leukemia. 2. Two of the isolated glycoproteins possess antiproteolytic activity. They appear to be formed by the interaction of neoplastic cells with an unidentified plasma precursor. Determination of the mode of formation of these 2 glycoproteins may shed new light on the relation between proteolysis and tumorigenesis.